Comparison of cyclocytidine and sympathetic nerve induced changes in norepinephrine and adrenoceptors in salivary glands.

Norepinephrine (NE) concentration of parotid and submandibular glands of young rats was reduced 51% and 39%, respectively at 1 h, and 60% and 47% at 2 h after i.p. administration of a single dose (500 mg/kg body weight) of the anti-tumor agent, cyclocytidine (CC). For adult rats, the reductions were 44% and 46%, respectively, at 1 h and 54% and 49% at 2 h. This decrease from controls was generally similar to the decrease induced following 1 and 2 h of electrical stimulation (square wave pulses of 4 V, 5 ms duration, and frequency of 16 Hz) of the sympathetic innervation to these glands (young rats, 59% and 58% at 1 h; 66% and 63% at 2 h; for adult rats, 51% and 55% at 1 h and 69% and 53% at 2 h for parotid and submandibular, respectively). The changes in density of beta-adrenoceptors induced by direct nerve stimulation also corresponded to the changes induced by CC (CC induced a decrease in parotid of 12%, compared with a decrease of 11% with electrical stimulation; a 15% and 18% reduction in number of beta-adrenoceptors of submandibular gland was found at 1 h after CC and electrical stimulation, respectively). Compelling evidence for the mechanism of CC action was thus established, showing that CC mimics effects of sympathetic nerve stimulation (inducing reduction in NE concentration and transient change in beta-adrenoceptor density) by causing release of NE from sympathetic nerve endings.